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Evaluation of the novel antiepileptic drug, AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys
- Source :
- European Journal of Pharmacology. 465:257-265
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 microg/kg/injection). When AWD 131-138 (10-100 microg/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 microg/kg i.v. AWD 131-138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low.
- Subjects :
- Male
Agonist
medicine.drug_class
Midazolam
medicine.medical_treatment
Nordazepam
Self Administration
Pharmacology
Injections, Intramuscular
Anxiolytic
Discrimination Learning
Cocaine
medicine
Animals
GABA-A Receptor Agonists
GABA Modulators
Saimiri
Chromatography, High Pressure Liquid
Benzodiazepine
Diazepam
Behavior, Animal
business.industry
Imidazoles
Anticonvulsant
Injections, Intravenous
Anticonvulsants
Self-administration
business
Reinforcement, Psychology
medicine.drug
Subjects
Details
- ISSN :
- 00142999
- Volume :
- 465
- Database :
- OpenAIRE
- Journal :
- European Journal of Pharmacology
- Accession number :
- edsair.doi.dedup.....bfa4d5c7f82b164eb20227acffc707ee